We will examine how eukaryotic mitochondria adapt to hypoxia using the yeast, Saccharomyces cerevisiae. Mitochondria from anaerobically grown S. cerevisiae are enlarged compared to mitochondria from aerobically grown cells. They also lack cytochromes, and are respiration- deficient. Similar changes are observed in mammalian mitochondria, particularly in mitochondria from ischemic hearts. Little is known about the molecular mechanisms regulating changes in mitochondrial structure and function in response to hypoxia. in addition, not much is known about how mitochondria function at oxygen levels between normoxia and hypoxia. These questions will be addressed in our proposed research. First, it will be determined how mitochondrial structure and function are affected by hypoxia, and at oxygen concentrations between normoxia and hypoxia. Second, proteins will be identified that regulate changes in mitochondrial structure and function in response to hypoxia. Third, it will be determined how genes that control mitochondrial structure and function, including OLE1, are regulated by oxygen. Specifically, it will be determined if either heme or reactive oxygen species (ROS) are involved in gene regulation. This research will provide insight into how mitochondria are affected by both hypoxia and ischemia.